Evaluation of NIH-IREP Lung Cancer Risk Model for Application to NIOSH-IREP 

Background 

The Energy Employees Occupational Illness Compensation Program Act of 2000, as 

amended (EEOICPA), provides a lump sum payment of $150,000 plus medical benefits 

to any covered U.S. nuclear weapons worker diagnosed with cancer if that cancer is 

determined to have been “at least as likely as not” caused by occupational exposure to 

ionizing radiation. The Department of Health and Human Services (HHS) is charged 

with developing and updating, as warranted, the scientific guidelines for assessing 

eligibility for compensation. The Office of Compensation Analysis and Support (OCAS) 

of the National Institute for Occupational Safety and Health (NIOSH) performs this 

function for HHS. 

HHS regulations (42 CFR Part 81) published in May 2002 established the guidelines for 

determining “probability of causation” under EEOICPA. Probability of causation, a term 

derived from the epidemiological concept of “assigned share,” is defined for purposes of 

compensation as the risk of cancer due to occupational exposure to ionizing radiation 

(i.e., excess relative risk, or “ERR”) divided by the total risk of cancer (1 + ERR.) Under 

EEOICPA, each cancer claim is individually evaluated via a computerized set of 

quantitative cancer risk assessment models. These risk models are embodied in a Webbased computational software package called NIOSH-IREP (Interactive RadioEpidemiological Program.) Employing Monte Carlo simulation sampling to account for 

the uncertainties of dose estimation, risk modeling, and the stochastic nature of cancer 

induction, NIOSH-IREP calculates the probability (expressed as a percentage) that a 

cancer was caused by radiation exposure incurred by a covered employee while in the 

performance of duty. 

A probability of causation of 50% or greater means that the claim merits compensation, 

i.e., that the cancer was “at least as likely as not” induced by radiation exposure. Each 

probability of causation result is unique, based upon data entered into NIOSH-IREP for 

that particular claim. Determinants of probability of causation include the type of cancer, 

amount and type of radiation dose, and other relevant factors (such as smoking history, if 

the cancer is of the lung, trachea, or bronchus.) In order to err on the side of the claimant, 

the upper 99th percentile credibility limit (akin to confidence limit) of probability of 

causation determines compensability. That is, if the upper 99th percentile credibility limit 

falls at 50 percent probability of causation or higher, the claim is deemed compensable. 

Discussion 

There are two different versions of IREP: NIOSH-IREP, the version maintained by 

NIOSH, and a separate version maintained by the National Cancer Institute (NCI) known 

as “NIH-IREP.” NIH-IREP was developed primarily to serve the needs of the 

Department of Veterans Affairs in adjudicating cancer claims filed by veterans exposed 

to radiation during military service. The cancer risk models in NIOSH-IREP, on the 

other hand, are intended to fit the characteristics and radiation exposures incurred by 
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civilian nuclear weapons workers. Most of the computerized risk models in both 

NIOSH-IREP and NIH-IREP are derived from a set of Radio-Epidemiological Tables 

created in 1985 by the National Institutes of Health (NIH) and periodically updated by 

NCI. The primary source of data for the Radio-Epidemiological Tables is the excess 

cancer incidence among Japanese atomic bomb survivors from World War II. 

Although NIOSH-IREP and NIH-IREP are similar in many ways, there are important 

differences in some risk models. Perhaps the most significant difference lies in the 

respective risk models for lung cancer (includes cancer of the trachea and bronchus) for 

exposure to radiation other than radon. Initially, the lung cancer models were identical in 

the two versions of IREP. However, NCI substantially revised the NIH-IREP lung 

cancer model in late 2003 to reflect a more recent analysis of lung cancer incidence 

among the Japanese atomic bomb survivors. The revision was based on published data 

(Pierce, et. al., 2003) and unpublished data (Land and Pierce, 2004.) NCI made a second 

revision to the NIH-IREP lung model in mid-2004 which affected only exposures to 

alpha radiation. This later revision was made in order to ensure consistency with the 

NIH-IREP documentation published by NCI in 2003. (“Report of the NCI-CDC 

Working Group to Revise the 1985 NIH Radioepidemiological Tables,” available via the 

NIOSH/OCAS Web site. See access instructions under “Online References.”) 

In the revised NIH-IREP lung model, ERR per unit dose is adjusted for age at exposure 

and age at diagnosis, whereas the NIOSH-IREP lung model does not adjust for these agedependent factors. Further, the NIH-IREP lung model is less heavily weighted toward a 

multiplicative interaction than is NIOSH-IREP in accounting for the interaction between 

cigarette smoking and lung cancer. Consequently, the same inputs entered into NIHIREP and NIOSH-IREP produce significantly different probabilities of causation for 

some exposure profiles. In terms of potential claim compensability, the main effect of 

the NCI revision is that NIH-IREP is generally more favorable to smokers and NIOSHIREP is generally more favorable to non-smokers. Other effects (gender-related, for 

example) are more difficult to generalize. 

A detailed analysis of the differences between the two IREP lung models can be found in 

the attached report (Apostoaei and Trabalka, 2004) commissioned by NIOSH from 

SENES Oak Ridge, Inc., the company that, under separate contracts with NIOSH and 

NCI, designed and programmed the IREP software packages according to the 

specifications of the two agencies. As noted in their report, SENES recommends that 

NIOSH adopt the NIH-IREP lung model for use in NIOSH-IREP. In SENES’ judgment, 

this change is warranted because the revised NIH-IREP model is based on four additional 

years of follow-up of the Japanese atomic bomb survivor cohort and, therefore, represents 

a more advanced state of scientific knowledge. As an alternative, SENES notes that 

NIOSH-IREP could be reprogrammed to run both IREP lung models and to output only 

the higher of the two probabilities of causation, thereby resolving differences in 

uncertainty by always erring on the side of the claimant. 

As noted earlier, NIOSH is charged with updating, as warranted, the scientific guidelines 

for assessing eligibility for compensation under EEOICPA. Potential modifications to 
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NIOSH-IREP cancer risk models must be evaluated by NIOSH for scientific merit and 

for their relevance and applicability to compensation claims. To help resolve this current 

issue, NIOSH is seeking input from outside experts. 

Question 

In your expert scientific judgment, should NIOSH adopt the NIH-IREP lung cancer risk 

model for exposures other than radon for use in NIOSH-IREP? If so, should the model 

be adopted intact, or should NIOSH modify it in some way to better fit the characteristics 

and radiation exposures of nuclear weapons workers covered under EEOICPA? 

Alternatively, should NIOSH-IREP be programmed to run both lung cancer models and 

to output only the higher probability of causation? Please provide the rationale for your 

conclusion. 

Report and remuneration 

Please submit your conclusion no later than February 14, 2005. To facilitate prompt 

reimbursement for your efforts, please include your SSN and postal mailing address and 

indicate the total number of days spent working on this project. NIOSH is authorized to 

provide $250.00 per day for time spent reviewing materials and preparing your report, 

not to exceed 10 days (maximum payment = $2500.00.) E-mail is an acceptable mode of 

transmission for your response and for your invoice for payment. 

Your report and invoice, as well as questions regarding any aspect of this project should 

be directed to: 

Russ Henshaw, MS 

Epidemiologist 

CDC/NIOSH/OCAS 

rih9@cdc.gov (e-mail) 

513-533-6812 (phone) 

4676 Columbia Pkwy., Mailstop C-46 

Cincinnati, OH 45226 

Acronyms

EEOICPA: Energy Employees Occupational Illness Compensation Program Act of 2000, 

as amended 

HHS: Department of Health and Human Services 

NCI: National Cancer Institute 

NIH: National Institutes of Health 

NIOSH: National Institute for Occupational Safety and Health 

OCAS: Office of Compensation Analysis and Support (an office of NIOSH created to 

carry out HHS responsibilities under EEOICPA) 
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Suggested References for Lung Model Evaluation (Attached)

Apostoaei AI, Trabalka JR. Differences in the estimation of lung cancer risk between 

NIOSH-IREP and NIH-IREP. SENES Oak Ridge, Inc., 2004 (unpublished report 

commissioned by NIOSH, 27 pages, PDF file) Note: Questions related to the SENES 

report may be addressed directly to Dr. F. Owen Hoffman, Director, SENES Oak 

Ridge, Inc. (phone: 865-483-6111; e-mail: sensor@senes.com ) 

Land CE, et.al. Draft Report of the NCI-CDC Working Group to Revise the 1985 NIH 

Radioepidemiological Tables, May 17, 2002, excerpts. (Note: This is an unpublished 

early draft of the report published in 2003 [see “Online References”] that formed the 

basis for the lung cancer model used in NIOSH-IREP; relevant pages are excerpted here. 

51 total pages, PDF file) 

Land CE, Pierce DA. Likelihood profile for parameter alpha used in computation of 

statistical uncertainty for ERR/Sv in NIH-IREP lung cancer model; re: Table IV.D.3, 

page 50, Report of the NCI-CDC Working Group to Revise the 1985 NIH 

Radioepidemiological Tables (Personal communication from Dr. Charles Land, 2004, 

titled by NIOSH for this reference. 5 pages, MS Word file) 

Pierce DA, Sharp GB, Mabuchi K. Joint effects of radiation and smoking on lung cancer 

risk among atomic bomb survivors. Radiation Research 159: 511-520, 2003 (10 pages, 

PDF file) 

Suggested Online References (Available via NIOSH/OCAS Web Page) 

The NIOSH-IREP software program is posted on the Web and is freely available to the 

public; no password is required. To access the software, navigate to the NIOSH/OCAS 

Web site at http://www.cdc.gov/niosh/ocas/default.html and then click on the link to the 

“Probability of Causation (NIOSH-IREP)” page, located in the “OCAS Directory” menu. 

A link to NIOSH-IREP can be found on that page. Direct links to documentation and 

help files are embedded throughout the series of NIOSH-IREP user screens. 

Additionally, a variety of technical references useful in evaluating the NIH-IREP and 

NIOSH-IREP lung models are accessible directly from the “Probability of Causation 

(NIOSH-IREP)” Web page. In particular, please note the following links: 

(1) Final Rule: Guidelines for Determining the Probability of Causation – 42 CFR 81 

(2) User’s Guide for the Interactive Radio-Epidemiological Program (NIOSH-IREP) 

(3) NIOSH-IREP Technical Documentation (In particular, see pages 32-33 and 57) 

(4) Report of the NCI-CDC Working Group to Revise the 1985 NIH 

Radioepidemiological Tables (i.e., the technical documentation for NIH-IREP, published 

in September 2003. In particular, see pages 26, 40-41, 50, and 69)